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SPINRAZA™ safely and effectively. See full prescribing information for
SPINRAZA.
SPINRAZA (nusinersen) injection, for intrathecal use
Initial U.S. Approval: 2016
__________________ INDICATIONS AND USAGE _________________
SPINRAZA is a survival motor neuron-2 (SMN2)-directed antisense
oligonucleotide indicated for the treatment of spinal muscular atrophy (SMA)
in pediatric and adult patients (1)
Laboratory Testing and Monitoring to Assess Safety (2.3)

At baseline and prior to each dose, obtain a platelet count, coagulation
laboratory testing, and quantitative spot urine protein testing
_____________ DOSAGE FORMS AND STRENGTHS ______________
Injection: 12 mg/5 mL (2.4 mg/mL) in a single-dose vial (3)
___________________ CONTRAINDICATIONS ___________________
None.
_______________ WARNINGS AND PRECAUTIONS _______________

_______________DOSAGE AND ADMINISTRATION ______________
SPINRAZA is administered intrathecally (2.1)

Dosing Information (2.1)

The recommended dosage is 12 mg (5 mL) per administration

Initiate SPINRAZA treatment with 4 loading doses; the first three
loading doses should be administered at 14-day intervals; the 4th loading
dose should be administered 30 days after the 3rd dose; a maintenance
dose should be administered once every 4 months thereafter
Important Preparation and Administration Instructions (2.2)

Allow to warm to room temperature prior to administration

Administer within 4 hours of removal from vial

Prior to administration, remove 5 mL of cerebrospinal fluid

Administer as intrathecal bolus injection over 1 to 3 minutes
Thrombocytopenia and Coagulation Abnormalities: Increased risk for
bleeding complications; testing required at baseline and before each dose
(5.1, 2.3)
Renal Toxicity: Quantitative spot urine protein testing required at
baseline and prior to each dose (5.2, 2.3)
___________________ ADVERSE REACTIONS ___________________
The most common adverse reactions that occurred in at least 20% of
SPINRAZA-treated patients and occurred at least 5% more frequently than in
control patients were lower respiratory infection, upper respiratory infection,
and constipation (6.1)
To report SUSPECTED ADVERSE REACTIONS, contact Biogen at 1800-456-2255 or FDA at 1-800-FDA-1088 or www.fda.gov/medwatch.
See 17 for PATIENT COUNSELING INFORMATION.
Revised: 05/2017
FULL PRESCRIBING INFORMATION: CONTENTS*
1
2
3
4
5
6
8
INDICATIONS AND USAGE
DOSAGE AND ADMINISTRATION
2.1 Dosing Information
2.2 Important Administration Instructions
2.3 Laboratory Testing and Monitoring to Assess Safety
DOSAGE FORMS AND STRENGTHS
CONTRAINDICATIONS
WARNINGS AND PRECAUTIONS
5.1
Thrombocytopenia and Coagulation Abnormalities
5.2
Renal Toxicity
ADVERSE REACTIONS
6.1 Clinical Trials Experience
6.2 Immunogenicity
6.3 Postmarketing Experience
USE IN SPECIFIC POPULATIONS
8.1 Pregnancy
8.2 Lactation
8.4 Pediatric Use
11
12
13
14
16
17
8.5 Geriatric Use
DESCRIPTION
CLINICAL PHARMACOLOGY
12.1 Mechanism of Action
12.2 Pharmacodynamics
12.3 Pharmacokinetics
NONCLINICAL TOXICOLOGY
13.1 Carcinogenesis, Mutagenesis, Impairment of Fertility
CLINICAL STUDIES
14.1 Clinical Trial in Infantile-Onset SMA
HOW SUPPLIED/STORAGE AND HANDLING
16.1 How Supplied
16.2 Storage and Handling
PATIENT COUNSELING INFORMATION
*Sections or subsections omitted from the full prescribing information are not
listed.
1
FULL PRESCRIBING INFORMATION
1
INDICATIONS AND USAGE
SPINRAZA is indicated for the treatment of spinal muscular atrophy (SMA) in pediatric and
adult patients.
2
DOSAGE AND ADMINISTRATION
2.1
Dosing Information
SPINRAZA is administered intrathecally by, or under the direction of, healthcare professionals
experienced in performing lumbar punctures.
Recommended Dosage
The recommended dosage is 12 mg (5 mL) per administration.
Initiate SPINRAZA treatment with 4 loading doses. The first three loading doses should be
administered at 14-day intervals. The 4th loading dose should be administered 30 days after the
3rd dose. A maintenance dose should be administered once every 4 months thereafter.
Missed Dose
If a loading dose is delayed or missed, administer SPINRAZA as soon as possible, with at least
14-days between doses and continue dosing as prescribed. If a maintenance dose is delayed or
missed, administer SPINRAZA as soon as possible and continue dosing every 4 months.
2.2
Important Preparation and Administration Instructions
SPINRAZA is for intrathecal use only.
Prepare and use SPINRAZA according to the following steps using aseptic technique. Each vial
is intended for single dose only.
Preparation





Store SPINRAZA in the carton in a refrigerator until time of use.
Allow the SPINRAZA vial to warm to room temperature (25o C/77o F) prior to
administration. Do not use external heat sources.
Inspect the SPINRAZA vial for particulate matter and discoloration prior to
administration. Do not administer SPINRAZA if visible particulates are observed or if
the liquid in the vial is discolored.
Withdraw 12 mg (5 mL) of SPINRAZA from the single-dose vial into a syringe and
discard unused contents of the vial.
Administer SPINRAZA within 4 hours of removal from vial.
Administration

Consider sedation as indicated by the clinical condition of the patient.



2.3
Consider ultrasound or other imaging techniques to guide intrathecal administration of
SPINRAZA, particularly in younger patients.
Prior to administration, remove 5 mL of cerebrospinal fluid.
Administer SPINRAZA as an intrathecal bolus injection over 1 to 3 minutes using a
spinal anesthesia needle [see Dosage and Administration (2.1)]. Do not administer
SPINRAZA in areas of the skin where there are signs of infection or inflammation.
Laboratory Testing and Monitoring to Assess Safety
Conduct the following laboratory tests at baseline and prior to each dose of SPINRAZA and as
clinically needed [see Warnings and Precautions (5.1, 5.2)]:
 Platelet count
 Prothrombin time; activated partial thromboplastin time
 Quantitative spot urine protein testing
3
DOSAGE FORMS AND STRENGTHS
Injection: 12 mg/5 mL (2.4 mg/mL) nusinersen as a clear and colorless solution in a single-dose
vial.
4
CONTRAINDICATIONS
None.
5
WARNINGS AND PRECAUTIONS
5.1
Thrombocytopenia and Coagulation Abnormalities
Coagulation abnormalities and thrombocytopenia, including acute severe thrombocytopenia,
have been observed after administration of some antisense oligonucleotides.
In a clinical study, 6 of 56 (11%) SPINRAZA-treated patients with normal or above normal
platelet levels at baseline developed a platelet level below the lower limit of normal, compared to
0 of 28 sham-procedure control patients. No patient had a platelet count less than 50,000 cells
per microliter in this study and no patient developed a sustained low platelet count despite
continued drug exposure.
Because of the risk of thrombocytopenia and coagulation abnormalities from SPINRAZA,
patients may be at increased risk of bleeding complications.
Perform a platelet count and coagulation laboratory testing at baseline and prior to each
administration of SPINRAZA and as clinically needed.
5.2
Renal Toxicity
Renal toxicity, including potentially fatal glomerulonephritis, has been observed after
administration of some antisense oligonucleotides.
SPINRAZA is present in and excreted by the kidney [see Clinical Pharmacology (12.3)]. In a
clinical study (mean treatment exposure 7 months), 17 of 51 (33%) SPINRAZA-treated patients
had elevated urine protein, compared to 5 of 25 (20%) sham-control patients. In a group of lateronset SMA patients (mean treatment exposure 34 months), 36 of 52 (69%) had elevated urine
protein. No elevations in serum creatinine or cystatin C were observed in these studies. Conduct
quantitative spot urine protein testing (preferably using a first morning urine specimen) at
baseline and prior to each dose of SPINRAZA. For urinary protein concentration greater than 0.2
g/L, consider repeat testing and further evaluation.
6
ADVERSE REACTIONS
The following serious adverse reactions are described in detail in other sections of the labeling:
6.1

Thrombocytopenia and Coagulation Abnormalities [see Warnings and Precautions (5.1)]

Renal Toxicity [see Warnings and Precautions (5.2)]
Clinical Trials Experience
Because clinical trials are conducted under widely varying conditions, adverse reaction rates
observed in the clinical trials of SPINRAZA cannot be directly compared to rates in clinical
trials of other drugs and may not reflect the rates observed in practice.
The data described below reflect exposure to SPINRAZA in 173 patients (50% male, 82%
Caucasian), including 120 exposed for at least 6 months and 83 exposed for at least 1 year. The
safety of SPINRAZA was studied in infants with symptomatic SMA, approximately 1 month to
8 months of age at study entry; in a sham-controlled trial (n=80 for SPINRAZA, n=41 for
control); in open-label studies in presymptomatic and symptomatic infants (n=37), and in openlabel studies in later onset patients (n=56, 2 to 15 years of age at study entry). In the controlled
study in symptomatic infants, 41 patients were exposed for at least 6 months and 19 patients
were exposed for at least 12 months.
In the controlled study, baseline disease characteristics were largely similar in the SPINRAZAtreated patients and sham-control patients except that SPINRAZA-treated patients at baseline
had a higher percentage compared to sham-control patients of paradoxical breathing (89% vs
66%), pneumonia or respiratory symptoms (35% vs 22%), swallowing or feeding difficulties
(51% vs 29%) and requirement for respiratory support (26% vs 15%).
In the controlled study, the most common adverse reactions that occurred in at least 20% of
SPINRAZA-treated patients and occurred at least 5% more frequently than in control patients
were lower respiratory infection, upper respiratory infection, and constipation. Serious adverse
reactions of atelectasis were more frequent in SPINRAZA-treated patients (14%) than in control
patients (5%). Because patients in the controlled study were infants, adverse reactions that are
verbally reported could not be assessed in this study.
Table 1.
Adverse Reactions that Occurred in at Least 5% of SPINRAZA Patients and
Occurred at Least 5% More Frequently or At Least 2 Times as Frequently Than
in Control Patients in the Controlled Study in Infants with Symptomatic SMA
SPINRAZA 12 mg1
Sham-Procedure Control
N=80
N=41
%
%
Lower respiratory infection2
43
29
Upper respiratory infection3
39
34
Constipation
30
22
Teething
14
7
Upper respiratory tract
congestion
6
2
Aspiration
5
2
Ear infection
5
2
Scoliosis
5
2
Adverse Reactions
1
Four loading doses followed by 12 mg (5 mL) once every 4 months
Includes pneumonia, bronchiolitis, pneumonia viral, respiratory syncytial virus bronchiolitis, lower respiratory tract infection, pneumonia
bacterial, bronchitis, bronchitis viral, pneumonia moraxella, pneumonia parainfluenzae viral, lower respiratory tract infection viral, lung infection,
pneumonia influenza, pneumonia pseudomonal, pneumonia respiratory syncytial viral
3
Includes upper respiratory tract infection, nasopharyngitis, rhinitis, pharyngitis, or tracheitis
2
In an open-label clinical study in infants with symptomatic SMA, severe hyponatremia was
reported in a patient treated with SPINRAZA requiring salt supplementation for 14 months.
Cases of rash were reported in patients treated with SPINRAZA. One patient, 8 months after
starting SPINRAZA treatment, developed painless red macular lesions on the forearm, leg, and
foot over an 8-week period. The lesions ulcerated and scabbed over within 4 weeks, and resolved
over several months. A second patient developed red macular skin lesions on the cheek and hand
ten months after the start of SPINRAZA treatment, which resolved over 3 months. Both cases
continued to receive SPINRAZA and had spontaneous resolution of the rash.
SPINRAZA may cause a reduction in growth as measured by height when administered to
infants, as suggested by observations from the controlled study. It is unknown whether any effect
of SPINRAZA on growth would be reversible with cessation of treatment.
The most common adverse events in the open-label studies in later onset patients were headache
(50%), back pain (41%) and post lumbar puncture syndrome (41%). Most of these events
occurred within 5 days of lumbar puncture. Other adverse events in these patients were
consistent with adverse reactions observed in the controlled study.
6.2
Immunogenicity
The immunogenic response to nusinersen was determined in 126 patients with baseline and postbaseline plasma samples evaluated for anti-drug antibodies (ADAs). Five (4%) patients
developed treatment-emergent ADAs, of which 3 were transient and 2 were considered to be
persistent. There are insufficient data to evaluate an effect of ADAs on clinical response, adverse
events, or the pharmacokinetic profile of nusinersen.
The detection of antibody formation is highly dependent on the sensitivity and specificity of the
assay. In addition, the observed incidence of antibody (including neutralizing antibody)
positivity in an assay may be influenced by several factors including assay methodology, sample
handling, timing of sample collection, concomitant medications and underlying disease. For
these reasons, comparison of the incidence of antibodies to SPINRAZA in the studies described
below with the incidence of antibodies in other studies or to other products may be misleading.
6.3
Postmarketing Experience
The following adverse reactions have been identified during post-approval use of SPINRAZA.
Because these reactions are reported voluntarily from a population of uncertain size, it is not
always possible to reliably estimate their frequency or establish a causal relationship to drug
exposure. Among patients treated with SPINRAZA, complications associated with lumbar
puncture including serious infections have been observed.
8
USE IN SPECIFIC POPULATIONS
8.1
Pregnancy
Risk Summary
There are no adequate data on the developmental risk associated with the use of SPINRAZA in
pregnant women. No adverse effects on embryofetal development were observed in animal
studies in which nusinersen was administered by subcutaneous injection to mice and rabbits
during pregnancy (see Data).
In the U.S. general population, the estimated background risk of major birth defects and
miscarriage in clinically recognized pregnancies is 2 to 4% and 15 to 20%, respectively. The
background risk of major birth defects and miscarriage for the indicated population is unknown.
Data
Animal Data
When nusinersen (0, 3, 10, or 25 mg/kg) was administered subcutaneously to male and female
mice every other day prior to and during mating and continuing in females throughout
organogenesis, no adverse effects on embryofetal development were observed. Subcutaneous
administration of nusinersen (0, 6, 12.6, or 25 mg/kg) to pregnant rabbits every other day
throughout organogenesis produced no evidence of embryofetal developmental toxicity.
8.2
Lactation
Risk Summary
There are no data on the presence of nusinersen in human milk, the effects on the breastfed
infant, or the effects of the drug on milk production. The developmental and health benefits of
breastfeeding should be considered along with the mother’s clinical need for SPINRAZA and
any potential adverse effects on the breastfed infant from SPINRAZA or from the underlying
maternal condition.
8.4
Pediatric Use
The safety and effectiveness of SPINRAZA in pediatric patients from newborn to 17 years have
been established [see Clinical Studies (14.1)].
Juvenile Animal Toxicity Data
In intrathecal toxicity studies in juvenile monkeys, administration of nusinersen (0, 0.3, 1, or 3
mg/dose for 14 weeks and 0, 0.3, 1, or 4 mg/dose for 53 weeks) resulted in brain histopathology
(neuronal vacuolation and necrosis/cellular debris in the hippocampus) at the mid and high doses
and acute, transient deficits in lower spinal reflexes at the high dose in each study. In addition,
possible neurobehavioral deficits were observed on a learning and memory test at the high dose
in the 53-week monkey study. The no-effect dose for neurohistopathology in monkeys (0.3
mg/dose) is approximately equivalent to the human dose when calculated on a yearly basis and
corrected for the species difference in CSF volume.
8.5
Geriatric Use
SMA is largely a disease of children and young adults; therefore, there is no geriatric experience
with SPINRAZA.
11
DESCRIPTION
SPINRAZA contains nusinersen, which is a modified antisense oligonucleotide, where the 2’hydroxy groups of the ribofuranosyl rings are replaced with 2’-O-2-methoxyethyl groups and the
phosphate linkages are replaced with phosphorothioate linkages. Nusinersen binds to a specific
sequence in the intron downstream of exon 7 of the SMN2 transcript. The structural formula is:
SPINRAZA is supplied as a sterile, preservative-free, colorless solution for intrathecal use in a
single-dose glass vial. Each 1 mL solution contains 2.4 mg of nusinersen (equivalent to 2.53 mg
of nusinersen sodium salt). Each 1 mL also contains calcium chloride dihydrate (0.21 mg) USP,
magnesium chloride hexahydrate (0.16 mg) USP, potassium chloride (0.22 mg) USP, sodium
chloride (8.77 mg) USP, sodium phosphate dibasic anhydrous (0.10 mg) USP, sodium phosphate
monobasic dihydrate (0.05 mg) USP, and Water for Injection USP. The product may contain
hydrochloric acid or sodium hydroxide to adjust pH. The pH is ~7.2.
The molecular formula of SPINRAZA is C234H323N61O128P17S17Na17 and the molecular weight is
7501.0 daltons.
12
CLINICAL PHARMACOLOGY
12.1
Mechanism of Action
SPINRAZA is an antisense oligonucleotide (ASO) designed to treat SMA caused by mutations
in chromosome 5q that lead to SMN protein deficiency. Using in vitro assays and studies in
transgenic animal models of SMA, SPINRAZA was shown to increase exon 7 inclusion in SMN2
messenger ribonucleic acid (mRNA) transcripts and production of full-length SMN protein.
12.2
Pharmacodynamics
Autopsy samples from patients (n=3) had higher levels of SMN2 messenger ribonucleic acid
(mRNA) containing exon 7 in the thoracic spinal cord compared to untreated SMA infants.
Cardiac Electrophysiology
In 121 patients with spinal muscular atrophy who received either SPINRAZA or sham-control,
QTcF values >500 ms and change from baseline values >60 ms were observed in 5% of patients
receiving SPINRAZA. Compared to the sham-control, there was no increase in the incidence of
cardiac adverse reactions associated with delayed ventricular repolarization in patients treated
with SPINRAZA.
12.3
Pharmacokinetics
Absorption
Intrathecal injection of SPINRAZA into the cerebrospinal fluid (CSF) allows nusinersen to be
distributed from the CSF to the target central nervous system (CNS) tissues. Following
intrathecal administration, trough plasma concentrations of nusinersen were relatively low,
compared to the trough CSF concentration. Median plasma Tmax values ranged from 1.7 to 6.0
hours. Mean plasma Cmax and AUC values increased approximately dose-proportionally up to a
dose of 12 mg.
Distribution
Autopsy data from patients (n=3) showed that SPINRAZA administered intrathecally was
distributed within the CNS and peripheral tissues, such as skeletal muscle, liver, and kidney.
Elimination
Metabolism
Nusinersen is metabolized via exonuclease (3’- and 5’)-mediated hydrolysis and is not a
substrate for, or inhibitor or inducer of CYP450 enzymes.
Excretion
The mean terminal elimination half-life is estimated to be 135 to 177 days in CSF, and 63 to 87
days in plasma. The primary route of elimination is likely by urinary excretion for nusinersen
and its chain-shortened metabolites. At 24 hours, only 0.5% of the administered dose was
recovered in the urine.
13
NONCLINICAL TOXICOLOGY
13.1
Carcinogenesis, Mutagenesis, Impairment of Fertility
Carcinogenesis
Long-term studies in animals to evaluate the carcinogenic potential of nusinersen have not been
performed.
Mutagenesis
Nusinersen demonstrated no evidence of genotoxicity in in vitro (Ames and chromosomal
aberration in CHO cells) and in vivo (mouse micronucleus) assays.
Impairment of Fertility
When nusinersen (0, 3, 10, or 25 mg/kg) was administered by subcutaneous injection to mice
every other day prior to and during mating and continuing in females throughout organogenesis,
no adverse effects on male or female fertility were observed.
14
CLINICAL STUDIES
The efficacy of SPINRAZA was demonstrated in a double-blind, sham-procedure controlled
clinical trial in symptomatic infantile-onset SMA patients and was supported by open-label
clinical trials conducted in presymptomatic and symptomatic SMA patients.
14.1
Clinical Trial in Infantile-Onset SMA
This study was a multicenter, randomized, double-blind, sham-procedure controlled study in 121
symptomatic infants ≤ 7 months of age at the time of first dose, diagnosed with SMA (symptom
onset before 6 months of age). Patients were randomized 2:1 to receive either SPINRAZA or
sham injection.
A planned interim efficacy analysis was conducted based on patients who died, withdrew, or
completed at least 183 days of treatment. Of the 82 patients included in the interim analysis, 44%
were male and 56% were female. Age at first treatment ranged from 30 to 262 days (median
181). Eighty-seven (87%) of subjects were Caucasian, 2% were Black, and 4% were Asian.
Length of treatment ranged from 6 to 442 days (median 261 days). Baseline demographics were
balanced between the SPINRAZA and control groups with the exception of age at first treatment
(median age 175 vs. 206 days, respectively). The SPINRAZA and control groups were balanced
with respect to gestational age, birth weight, disease duration, and SMN2 copy number (2 copies
in 98% of subjects in boths groups). Median disease duration was 14 weeks. There was some
imbalance in age at symptom onset with 88% of subjects in the SPINRAZA group and 77% in
the control group experiencing symptoms within the first 12 weeks of life.
The primary endpoint assessed at the time of interim analysis was the proportion of responders:
patients with an improvement in motor milestones according to Section 2 of the Hammersmith
Infant Neurologic Exam (HINE). This endpoint evaluates seven different areas of motor
milestone development, with a maximum score between 2-4 points for each, depending on the
milestone, and a total maximum score of 26. A treatment responder was defined as any patient
with at least a 2-point increase (or maximal score of 4) in ability to kick (consistent with
improvement by at least 2 milestones), or at least a 1-point increase in the motor milestones of
head control, rolling, sitting, crawling, standing or walking (consistent with improvement by at
least 1 milestone). To be classified as a responder, patients needed to exhibit improvement in
more categories of motor milestones than worsening. Of the 82 patients who were eligible for
the interim analysis, a statistically significantly greater percentage of patients achieved a motor
milestone response in the SPINRAZA group compared to the sham-control group (see Table 2).
Figure 1 is a descriptive display of the distribution of net change from baseline in the total motor
milestone score for Section 2 of the HINE.
Although not statistically controlled for multiple comparisons at the interim analysis, the study
also assessed treatment effects on the Children’s Hospital of Philadelphia Infant Test of
Neuromuscular Disorders (CHOP-INTEND), which is an evaluation of motor skills in patients
with infantile-onset SMA. The CHOP-INTEND results are displayed in Table 2.
Table 2.
Motor Milestone Response and CHOP-INTEND Results
Endpoint
Motor Milestone (HINE Section 2)
Achievement of a motor milestone response
SPINRAZA-treated
patients (n=52)1
21 (40%)
p<0.0001
CHOP-INTEND Improvement from Baseline2
At least 4-points
33 (63%)
CHOP-INTEND Worsening from Baseline2
At least 4-points
2 (4%)
Sham-control
patients (n=30)1
0 (0%)
1 (3%)
12 (40%)
1
Analyses included all subjects who were alive with the opportunity for at least a 6-month (Day 183) assessment and
all subjects who died or withdrew from the study at the time of the interim analysis
2
Not statistically controlled for multiple comparisons at interim analysis
Figure 1. Net Change from Baseline in Total Motor Milestone Score (HINE) by Percent of
Subjects in the Interim Efficacy Set*
*For subjects who were alive and ongoing in the study, the change in total motor milestone score was calculated at
the later of Day 183, Day 302, or Day 394.
The results of the controlled trial in infantile-onset SMA patients were supported by open-label
uncontrolled trials conducted in symptomatic SMA patients who ranged in age from 30 days to
15 years at the time of first dose, and in presymptomatic patients, who ranged in age from 8 days
to 42 days at the time of first dose. The patients in these studies had or were likely to develop
Type 1, 2, or 3 SMA. Some patients achieved milestones such as ability to sit unassisted, stand,
or walk when they would otherwise be unexpected to do so, maintained milestones at ages when
they would be expected to be lost, and survived to ages unexpected considering the number of
SMN2 gene copies of patients enrolled in the studies.
The overall findings of the controlled trial in infantile-onset SMA and the open-label
uncontrolled trials support the effectiveness of SPINRAZA across the range of SMA patients,
and appear to support the early initiation of treatment with SPINRAZA.
16
HOW SUPPLIED/STORAGE AND HANDLING
16.1
How Supplied
SPINRAZA injection is a sterile, clear and colorless solution supplied as a 12 mg/5 mL (2.4
mg/mL) solution in a single-dose glass vial free of preservatives. The NDC is 64406-058-01.
16.2
Storage and Handling
Store in a refrigerator between 2°C to 8°C (36°F to 46°F) in the original carton to protect from
light. Do not freeze.
SPINRAZA should be protected from light and kept in the original carton until time of use.
If no refrigeration is available, SPINRAZA may be stored in its original carton, protected from
light at or below 30oC (86oF) for up to 14 days.
Prior to administration, unopened vials of SPINRAZA can be removed from and returned to the
refrigerator, if necessary. If removed from the original carton, the total combined time out of
refrigeration should not exceed 30 hours at a temperature that does not exceed 25oC (77oF).
17
PATIENT COUNSELING INFORMATION
Thrombocytopenia and Coagulation Abnormalities
Inform patients and caregivers that SPINRAZA could increase the risk of bleeding. Inform
patients and caregivers of the importance of obtaining blood laboratory testing at baseline and
prior to each dose to monitor for signs of increased potential for bleeding. Instruct patients and
caregivers to seek medical attention if unexpected bleeding occurs [see Warnings and
Precautions (5.1)].
Renal Toxicity
Inform patients and caregivers that SPINRAZA could cause renal toxicity. Inform patients and
caregivers of the importance of obtaining urine testing at baseline and prior to each dose to
monitor for signs of potential renal toxicity [see Warnings and Precautions (5.2)].
49655-02
Manufactured for:
Biogen Inc.
Cambridge, MA 02142
SPINRAZA is a trademark of Biogen.
© Biogen 2016-2017